US2936310A - Process of preparing macrocyclic - Google Patents
Process of preparing macrocyclic Download PDFInfo
- Publication number
- US2936310A US2936310A US2936310DA US2936310A US 2936310 A US2936310 A US 2936310A US 2936310D A US2936310D A US 2936310DA US 2936310 A US2936310 A US 2936310A
- Authority
- US
- United States
- Prior art keywords
- glycerol
- hydroxy
- acid
- oxa
- pentadecanolide
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Expired - Lifetime
Links
- 238000000034 method Methods 0.000 title description 12
- PEDCQBHIVMGVHV-UHFFFAOYSA-N glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 claims description 144
- 229920000642 polymer Polymers 0.000 claims description 26
- 150000002596 lactones Chemical class 0.000 claims description 24
- 239000003054 catalyst Substances 0.000 claims description 22
- 238000010438 heat treatment Methods 0.000 claims description 16
- BVKZGUZCCUSVTD-UHFFFAOYSA-N Carbonic acid Chemical compound OC(O)=O BVKZGUZCCUSVTD-UHFFFAOYSA-N 0.000 claims description 8
- WQEPLUUGTLDZJY-UHFFFAOYSA-N Pentadecanoic acid Chemical compound CCCCCCCCCCCCCCC(O)=O WQEPLUUGTLDZJY-UHFFFAOYSA-N 0.000 claims description 8
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 8
- 230000000875 corresponding Effects 0.000 claims description 6
- OFBQJSOFQDEBGM-UHFFFAOYSA-N pentane Chemical compound CCCCC OFBQJSOFQDEBGM-UHFFFAOYSA-N 0.000 claims description 6
- 239000011541 reaction mixture Substances 0.000 claims description 6
- UHHRXYIEDZGENE-UHFFFAOYSA-N 11-(3-hydroxypropoxy)undecanoic acid Chemical compound OCCCOCCCCCCCCCCC(O)=O UHHRXYIEDZGENE-UHFFFAOYSA-N 0.000 claims description 4
- KAIQFVRSSKPNJF-UHFFFAOYSA-N 11-(4-hydroxybutoxy)undecanoic acid Chemical compound OCCCCOCCCCCCCCCCC(O)=O KAIQFVRSSKPNJF-UHFFFAOYSA-N 0.000 claims description 4
- 238000004519 manufacturing process Methods 0.000 claims description 4
- 101700031574 TROL Proteins 0.000 claims 2
- 101700037823 str4 Proteins 0.000 claims 2
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 32
- 238000006243 chemical reaction Methods 0.000 description 26
- FKUPPRZPSYCDRS-UHFFFAOYSA-N Cyclopentadecanolide Chemical compound O=C1CCCCCCCCCCCCCCO1 FKUPPRZPSYCDRS-UHFFFAOYSA-N 0.000 description 24
- 238000009835 boiling Methods 0.000 description 18
- KWYUFKZDYYNOTN-UHFFFAOYSA-M potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 18
- 238000002360 preparation method Methods 0.000 description 16
- 125000004122 cyclic group Chemical group 0.000 description 12
- 239000000178 monomer Substances 0.000 description 12
- RWGFKTVRMDUZSP-UHFFFAOYSA-N Cumene Chemical compound CC(C)C1=CC=CC=C1 RWGFKTVRMDUZSP-UHFFFAOYSA-N 0.000 description 10
- 238000005886 esterification reaction Methods 0.000 description 10
- OKKJLVBELUTLKV-UHFFFAOYSA-N methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 8
- 239000000203 mixture Substances 0.000 description 8
- FXBOKASTQKMONI-UHFFFAOYSA-N 2-methyl-5-(2-methylphenoxy)benzenesulfonic acid Chemical compound CC1=CC=CC=C1OC1=CC=C(C)C(S(O)(=O)=O)=C1 FXBOKASTQKMONI-UHFFFAOYSA-N 0.000 description 6
- 229910052783 alkali metal Inorganic materials 0.000 description 6
- 150000001340 alkali metals Chemical class 0.000 description 6
- 238000004821 distillation Methods 0.000 description 6
- 150000004679 hydroxides Chemical class 0.000 description 6
- 150000001261 hydroxy acids Chemical class 0.000 description 6
- 150000003839 salts Chemical class 0.000 description 6
- 239000011780 sodium chloride Substances 0.000 description 6
- 239000000243 solution Substances 0.000 description 6
- MRMOPGVGWFNHIN-UHFFFAOYSA-N 1,6-dioxacycloheptadecan-7-one Chemical compound O=C1CCCCCCCCCCOCCCCO1 MRMOPGVGWFNHIN-UHFFFAOYSA-N 0.000 description 4
- 239000003513 alkali Substances 0.000 description 4
- 239000007795 chemical reaction product Substances 0.000 description 4
- 150000001875 compounds Chemical class 0.000 description 4
- 150000002148 esters Chemical class 0.000 description 4
- 239000012442 inert solvent Substances 0.000 description 4
- 238000002844 melting Methods 0.000 description 4
- 239000000843 powder Substances 0.000 description 4
- 239000011734 sodium Substances 0.000 description 4
- WQDUMFSSJAZKTM-UHFFFAOYSA-N sodium methoxide Chemical compound [Na+].[O-]C WQDUMFSSJAZKTM-UHFFFAOYSA-N 0.000 description 4
- 238000007711 solidification Methods 0.000 description 4
- 239000002904 solvent Substances 0.000 description 4
- YXFVVABEGXRONW-UHFFFAOYSA-N toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 4
- BZUNJUAMQZRJIP-UHFFFAOYSA-N 15-hydroxypentadecanoic acid Chemical compound OCCCCCCCCCCCCCCC(O)=O BZUNJUAMQZRJIP-UHFFFAOYSA-N 0.000 description 2
- NKASEPJANRVKDD-UHFFFAOYSA-N 2-hydroxypentadecanoic acid Chemical compound CCCCCCCCCCCCCC(O)C(O)=O NKASEPJANRVKDD-UHFFFAOYSA-N 0.000 description 2
- 210000001736 Capillaries Anatomy 0.000 description 2
- 241001292274 Eumenes Species 0.000 description 2
- IPCSVZSSVZVIGE-UHFFFAOYSA-N Palmitic acid Chemical compound CCCCCCCCCCCCCCCC(O)=O IPCSVZSSVZVIGE-UHFFFAOYSA-N 0.000 description 2
- 235000021314 Palmitic acid Nutrition 0.000 description 2
- 239000002253 acid Substances 0.000 description 2
- 230000001476 alcoholic Effects 0.000 description 2
- 150000001298 alcohols Chemical class 0.000 description 2
- 150000001339 alkali metal compounds Chemical class 0.000 description 2
- 238000005904 alkaline hydrolysis reaction Methods 0.000 description 2
- 239000007864 aqueous solution Substances 0.000 description 2
- OYPRJOBELJOOCE-UHFFFAOYSA-N calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 2
- 239000011575 calcium Substances 0.000 description 2
- 229910052791 calcium Inorganic materials 0.000 description 2
- 125000004432 carbon atoms Chemical group C* 0.000 description 2
- 239000000539 dimer Substances 0.000 description 2
- 238000005485 electric heating Methods 0.000 description 2
- 238000005194 fractionation Methods 0.000 description 2
- 125000000524 functional group Chemical group 0.000 description 2
- 125000005842 heteroatoms Chemical group 0.000 description 2
- 239000012535 impurity Substances 0.000 description 2
- WHXSMMKQMYFTQS-UHFFFAOYSA-N lithium Chemical compound [Li] WHXSMMKQMYFTQS-UHFFFAOYSA-N 0.000 description 2
- 229910052744 lithium Inorganic materials 0.000 description 2
- 229910052751 metal Inorganic materials 0.000 description 2
- 239000002184 metal Substances 0.000 description 2
- CTQNGGLPUBDAKN-UHFFFAOYSA-N o-xylene Chemical compound CC1=CC=CC=C1C CTQNGGLPUBDAKN-UHFFFAOYSA-N 0.000 description 2
- MYMOFIZGZYHOMD-UHFFFAOYSA-N oxygen Chemical compound O=O MYMOFIZGZYHOMD-UHFFFAOYSA-N 0.000 description 2
- 229910052760 oxygen Inorganic materials 0.000 description 2
- 239000001301 oxygen Substances 0.000 description 2
- WQEPLUUGTLDZJY-UHFFFAOYSA-M pentadecanoate Chemical compound CCCCCCCCCCCCCCC([O-])=O WQEPLUUGTLDZJY-UHFFFAOYSA-M 0.000 description 2
- FVGBHSIHHXTYTH-UHFFFAOYSA-N pentane-1,1,1-triol Chemical compound CCCCC(O)(O)O FVGBHSIHHXTYTH-UHFFFAOYSA-N 0.000 description 2
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 2
- 229910052700 potassium Inorganic materials 0.000 description 2
- 239000011591 potassium Substances 0.000 description 2
- 239000000047 product Substances 0.000 description 2
- 238000001953 recrystallisation Methods 0.000 description 2
- 238000009877 rendering Methods 0.000 description 2
- 238000000926 separation method Methods 0.000 description 2
- KEAYESYHFKHZAL-UHFFFAOYSA-N sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 2
- 229910052708 sodium Inorganic materials 0.000 description 2
- 239000000126 substance Substances 0.000 description 2
- LSNNMFCWUKXFEE-UHFFFAOYSA-N sulfonic acid Chemical compound OS(O)=O LSNNMFCWUKXFEE-UHFFFAOYSA-N 0.000 description 2
- 150000004072 triols Chemical class 0.000 description 2
- 239000008096 xylene Substances 0.000 description 2
Images
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D321/00—Heterocyclic compounds containing rings having two oxygen atoms as the only ring hetero atoms, not provided for by groups C07D317/00 - C07D319/00
Definitions
- ATTORNEY PROCESS F PREPARING MAC-ROCYCLIC LACTONES Muus G. J. Beets and Harm van Essen, Hilversum, Netherlands, assiguors, by mesne assignments, to Polak & Sclgwarz International N.V., a corporation of the Nether nds Application June 6, 1955, Serial No. 513,431 Claims priority, application Netherlands July 2, 1954 3 Claims. (Cl. 260-340.2)
- the present invention relates to a process of preparing macrocyclic lactones.
- Macrocyclic lactones i.e. cyclic esters of hydroxy carboxylic acids, in which both functional groups are separated by a chain of 20 carbon atoms, which may be alternated by hetero atoms, such as oxygen, hav great value as odoriferous substances.
- macrocyclic lactones are prepared in very high yields from the easily available polymeric esters of hydroxy carboxylic acids by heating these polymers, preferably in vacuo, in the presence of re-esterification catalysts, such as alkali metal alcoholates, hydroxides or salts and of a high boiling compound which is not or substantially not miscible with the desired cyclic monomer and which is capable of withdrawing this monomer from the reaction mixture by codistillation at the rate at which it is formed.
- re-esterification catalysts such as alkali metal alcoholates, hydroxides or salts and of a high boiling compound which is not or substantially not miscible with the desired cyclic monomer and which is capable of withdrawing this monomer from the reaction mixture by codistillation at the rate at which it is formed.
- codistillation components are trivalent alcohols such as glycerol and pentane triol-l.2.5.
- a suitable manner of preparing polymeric esters is the heating of the hydroxy acid in an inert solvent forming an azeotrope with water or boiling at a sutficiently high temperature to ensure continuous removal of 'water and, in the presence of an esterification catalyst, in an apparatus rendering continuous removal of reaction water possible. This reaction is continued until the calculated amount of reaction water has been collected and the acid number of the mixture has fallen to or substantially to the value corresponding to the added esterification catalyst.
- Mixed polymers may also he prepared in analogous manner by heating the hydroxy acid, together with an arbitrary amount of a high-boiling alcoholic component, e.g. glycerol, inan inert solvent forming an azeotrope with water or boiling at a sufficiently high temperature to ensure continuous removal of water, and in the presence of an esterifica'tion catalyst, the formed reaction water being distilled off continuously with the solvent.
- a high-boiling alcoholic component e.g. glycerol
- inan inert solvent forming an azeotrope with water or boiling at a sufficiently high temperature to ensure continuous removal of water, and in the presence of an esterifica'tion catalyst, the formed reaction water being distilled off continuously with the solvent.
- a quantity of a re-esteiification catalyst is added to the solution obtained of the polymer or mixed polymer.
- a re-esteiification catalyst for this purpose alcoholates, hydroxides or salts of alkali or earth alkali metals may be used.
- the catalyst is alkaline, it may also serve for theneutralisation of the esterification catalyst added for the polymerisation, whereupon the solvent is distilled off and replaced by a high boiling compound which can be used as a codistillation component for the cyclic monomer, e.g. glycerol.
- the entire treatment may be carried out in a technically very simple mannerv in an apparatus which is diagrammatically represented in the annexed figure.
- the polymer together'with the re-esterification catalyst and the codistillation component, is brought into a reaction flask 1 surrounded by an electric heating jacket and provided with a capillary and a thermometer and States Patent 3 tion component, until the p 1 hour.
- the lateral tube 5 is filled with the codistillation component.
- the codistillation component distils simultaneously with the cyclic monomer formed through the distillation column 2 and th cooler 3.
- the distillate is collected in 4, where it is divided into two layers, of which the lower layer, consisting of the codistillation component, recycles continuously to the reaction vessel, via 5, whereas the upper layer, the cyclic monomer, flows continuously to the recipient 6. If necessary, small quantities of the codistillation component may be supplied through the dropping fiunnel 7 without disturbing the vacuum.
- a very simple embodiment, in which the polymerisation and depolymerisation can be carried out without interruption in the same apparatus is obtained when the a hydroxy acid is brought into the reaction flask 1 and this necessary for the following treatment, namely the depolymerisation reaction, e.g. potassium hydroxide in powder form or aqueous solution, and of the codistillaand the reaction Water formed has been entirely removed.
- the depolymerisation reaction e.g. potassium hydroxide in powder form or aqueous solution
- the codistillaand the reaction Water formed has been entirely removed.
- the heating is continued without interruption, the desired macrocyclic lactone being formed under depolymerisation.
- the product thus obtained consists practically entirely of the cyclic monomer. amount of dimer and other impurities by fractionated distillation.
- EXAMPLE 1 Preparation of 12-0xa-hexadecan0lide hexadecanoic acid and 3 g. of toluene 'sulphonic acid are boiled in 624 cm. of cumene at a water separatoruntil no water distils over anymore. Duration approximately 12.5 g. of sodium methylate and 72 g. of glycerol.
- the eumene is distilled oif completely, the apparatus represented in the figure is applied and one heats under a vacuum of 4-5 mm. until no or only a little-of oxa---
- the temperature in the reacting mixture amounts to 188-l92 C.
- the distillate is separated from glycerol, washed with water for the removal of traces of glycerol and distilled. The yield amounts to approximately 80% of the theory.
- the yield amounts to 5.100 kg. of 12-oxa-hex-adecanolide or 86.4% of the theory.
- the pentadecanolide is separated in the heat from 4 of glycerol in which 3 g. of lithium have been dissolved in accordance with one of the Examples 1 or 2.
- glycerol it is washed with water for the removal of traces of glycerol and fractionated in vacuo. Fractions with a starting solidification point of 35 C. or higher are collected. The yield amounts to approximately 80%.
- alkaline hydrolysis and recrystallisation alternating amounts of hydroxy pentadecanoic acid may be recovered from the residue of the cyclisation, owing to which the total yield is raised to between 85 and 90%.
- EXAMPLE 8 7 Preparation of pentadecanolide
- the polymer of IS-hydroxy-pentadecanoic acid is prepared according to Example 3.
- the yield is lower than when using alkali metal compounds.
- EXAMPLE 10 Preparation of pentadecanolide pletely and cyclisizes according to Example 1. When no or substantially no pentadecanolide codistils anymore with pentane triol the lactone is separated from the triol and distilled. 181 g. of pentadecanolide are obtained. Melting point 35 C. Yield 75 of the theory.
- a process for preparing a macrocyclic lactone selected from the group consisting of pentadecanolide, 12- oxa-hexadecanolide and l2-oxa-pentadecanolide comprising the steps of heating a polymer of a hydroxy carboxylic acid selected from the group consisting of IS-hydroxy pentadecanoic acid, l-hydroxy-12-oxa-hexadecanoic acid and 15-hydroxy-12-oxa-pentadecanoic acid, in the presence of an alkaline catalyst and a trihydric alcohol selected from the group consisting of glycerol and pentane triol-1.2.5 to depolyrnerize the polymer, and removing the corresponding lactone from the reaction mixture'by codistillation with the trihydric alcohol at the rate at which it is formed. 7 V 2.
- the alkaline catalyst is selected from the group consisting of alcoholates
- hydroxides and salts of alkali and earth'alkali metals are hydroxides and salts of alkali and earth'alkali metals.
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Description
May 10, 1960 M. G. J. BEETS ETAL 2,936,310
PROCESS OF PREPARING MACROCYCLIC LACTONES Filed June 6, 1955 INVENTOR. Muus GJ. BEETS re/farm VAN ESSEN y j../o4n
ATTORNEY PROCESS F PREPARING MAC-ROCYCLIC LACTONES Muus G. J. Beets and Harm van Essen, Hilversum, Netherlands, assiguors, by mesne assignments, to Polak & Sclgwarz International N.V., a corporation of the Nether nds Application June 6, 1955, Serial No. 513,431 Claims priority, application Netherlands July 2, 1954 3 Claims. (Cl. 260-340.2)
The present invention relates to a process of preparing macrocyclic lactones.
Macrocyclic lactones, i.e. cyclic esters of hydroxy carboxylic acids, in which both functional groups are separated by a chain of 20 carbon atoms, which may be alternated by hetero atoms, such as oxygen, hav great value as odoriferous substances.
In accordance with the present invention, macrocyclic lactones are prepared in very high yields from the easily available polymeric esters of hydroxy carboxylic acids by heating these polymers, preferably in vacuo, in the presence of re-esterification catalysts, such as alkali metal alcoholates, hydroxides or salts and of a high boiling compound which is not or substantially not miscible with the desired cyclic monomer and which is capable of withdrawing this monomer from the reaction mixture by codistillation at the rate at which it is formed. Very efficient examples of such codistillation components are trivalent alcohols such as glycerol and pentane triol-l.2.5.
A suitable manner of preparing polymeric esters is the heating of the hydroxy acid in an inert solvent forming an azeotrope with water or boiling at a sutficiently high temperature to ensure continuous removal of 'water and, in the presence of an esterification catalyst, in an apparatus rendering continuous removal of reaction water possible. This reaction is continued until the calculated amount of reaction water has been collected and the acid number of the mixture has fallen to or substantially to the value corresponding to the added esterification catalyst.
Mixed polymers may also he prepared in analogous manner by heating the hydroxy acid, together with an arbitrary amount of a high-boiling alcoholic component, e.g. glycerol, inan inert solvent forming an azeotrope with water or boiling at a sufficiently high temperature to ensure continuous removal of water, and in the presence of an esterifica'tion catalyst, the formed reaction water being distilled off continuously with the solvent. I
Thereupon a quantity of a re-esteiification catalyst is added to the solution obtained of the polymer or mixed polymer. For this purpose alcoholates, hydroxides or salts of alkali or earth alkali metals may be used. When the catalyst is alkaline, it may also serve for theneutralisation of the esterification catalyst added for the polymerisation, whereupon the solvent is distilled off and replaced by a high boiling compound which can be used as a codistillation component for the cyclic monomer, e.g. glycerol.
7 Finally one heats for the depolymerisation of the polymer, preferably in vacuo.
The entire treatment may be carried out in a technically very simple mannerv in an apparatus which is diagrammatically represented in the annexed figure.
The polymer, together'with the re-esterification catalyst and the codistillation component, is brought into a reaction flask 1 surrounded by an electric heating jacket and provided with a capillary and a thermometer and States Patent 3 tion component, until the p 1 hour.
2 the lateral tube 5 is filled with the codistillation component.
During heating in vacuo the codistillation component distils simultaneously with the cyclic monomer formed through the distillation column 2 and th cooler 3. The distillate is collected in 4, where it is divided into two layers, of which the lower layer, consisting of the codistillation component, recycles continuously to the reaction vessel, via 5, whereas the upper layer, the cyclic monomer, flows continuously to the recipient 6. If necessary, small quantities of the codistillation component may be supplied through the dropping fiunnel 7 without disturbing the vacuum.
A very simple embodiment, in which the polymerisation and depolymerisation can be carried out without interruption in the same apparatus is obtained when the a hydroxy acid is brought into the reaction flask 1 and this necessary for the following treatment, namely the depolymerisation reaction, e.g. potassium hydroxide in powder form or aqueous solution, and of the codistillaand the reaction Water formed has been entirely removed. Hereupon the heating is continued without interruption, the desired macrocyclic lactone being formed under depolymerisation.
The product thus obtained consists practically entirely of the cyclic monomer. amount of dimer and other impurities by fractionated distillation.
The method described here enables macrocyclic lactones in very high yields.
The invention is elucidated by the following examples.
EXAMPLE 1 Preparation of 12-0xa-hexadecan0lide hexadecanoic acid and 3 g. of toluene 'sulphonic acid are boiled in 624 cm. of cumene at a water separatoruntil no water distils over anymore. Duration approximately 12.5 g. of sodium methylate and 72 g. of glycerol.
The eumene is distilled oif completely, the apparatus represented in the figure is applied and one heats under a vacuum of 4-5 mm. until no or only a little-of oxa--- During the dehexadecanolide codistils with glycerol. polymerisation the temperature in the reacting mixture amounts to 188-l92 C. The distillate is separated from glycerol, washed with water for the removal of traces of glycerol and distilled. The yield amounts to approximately 80% of the theory.
Boiling point at 3 mm. 150 C.; 12 1.4676; d
EXAMPLE 2 Preparation of IZ-OxaJzexadeCanOIid 6.32 kg. of 16-hydroxy-12-oxa-hexadecanoic acid with 0.807 kgpof glycerol and 0.129 kg. of 50% potassium hydroxide solution are introduced into the apparatus:
represented in the figure and one beats in a vacuum of 14-16 mm. whilst gradually increasing the temperature to 180, until the reaction water has been distilled off substantially entirely. One switches over to high vacuum and continues the heating until the reaction is complete. Hereupon the tube, 5 is filled with glyceroland, the cyclisation is carried out in accordance with Example;
1. The yield amounts to 5.100 kg. of 12-oxa-hex-adecanolide or 86.4% of the theory.
EXAMPLE 3 Preparation of I2-0xa-pentadecanolide pentadecanoic acid and 2 g. of toluene sulphonic acid is Patented May 10, 1960 polymerisation is completed It can be freed from a small one to prepare One cools to approximately C. and adds boiled in 500 cm. of cumene until no water separates 01f anymore. 43 g. of glycerol in which 1.5 g. of Na have been dissolved are added, the cumene is distilled 4 kg. of 15-hydroxy pentadecanoic acid with 0.54 kg. of glycerol and 44 g. of potassium hydroxide powder are introduced into the apparatus represented in the figureand one heats Whilst polymerising in accordance with Example2. When the reaction water has been driven out completely the lateral tube 5 is filled with glycerol and cyclisation is effected in accordance with Example 1. By distillation of the reaction product 2996.5 g. of pentadecanolide with solidification point 358 or 80.5% of the theory are obtained.
= EXAMPLE 5 Preparation of pentadecanolide 702 g. (2.72 mols) of lfi-hydroxy pentadecanoic acid are polymerized by boiling in an automatic water separator. in the presence of 6 g. of toluene sulphonic acid and 1375 cm. of cumene. After approximately 1 hour theereaction is complete. One cools to approximately 110 C. and adds 22 g. of sodium.methylate and 92 g.
of glycerol. The cumene is distilled off completely and depolymerisation is effected in a vacuum of 4-5 mm. until only little or no pentadecanolide codistils with the glycerol. During this period the temperature in the reaction'mixture amounts to 195-205 C.
'The pentadecanolide is separated in the heat from 4 of glycerol in which 3 g. of lithium have been dissolved in accordance with one of the Examples 1 or 2. One
glycerol, it is washed with water for the removal of traces of glycerol and fractionated in vacuo. Fractions with a starting solidification point of 35 C. or higher are collected. The yield amounts to approximately 80%. By alkaline hydrolysis and recrystallisation alternating amounts of hydroxy pentadecanoic acid may be recovered from the residue of the cyclisation, owing to which the total yield is raised to between 85 and 90%.
EXAMPLE 6 Preparation of pentadecanolide A mixture of:
387. g. (1.5 mols) of IS-hydroxy pentadecanoic acid 92 g. (1 mol) of glycerol 3 g. of toluene sulphonic acid and 500 cm? of xylene 580.5 g. (2.25 mols) of l5-hydroxy pentadecanoic acid are polymerized and cyclisized with the aid of 150 g.
depolymerizes in vacuo and works up according to one of the preceding examples. The yield amounts to of the theory.
EXAMPLE 8 7 Preparation of pentadecanolide The polymer of IS-hydroxy-pentadecanoic acid is prepared according to Example 3.
At l00l10 C. a solution of 12.5 g. of calcium in 125 g. of glycerol, prepared by dissolving the metal in methanol, adding glycerol and distilling off the methanol, is added.
One depolymerizes at a temperature of' 200-205 C. until no pentadecanolide codistils anymore with glycerol. One works up and fractionates according to Example 3.
The yield is lower than when using alkali metal compounds.
' EXAMPLE 9 Preparation of pentadecanolide 218 g. (0.84 mol) of 1S-hydroxy-pentadecanoic acid.
are converted into the polymer with g. of glycerol and 37 g. of potassium 14-hyd1oxy tetradecane-l-carboxylate according to Examples 2 and 4; One depolymerizes in vacuo according to one of the preceding examples. After separation of the glycerol and fractionation of the reaction product the yield amounts to 81% of the theory. Melting point 35.2 C.
EXAMPLE 10 Preparation of pentadecanolide pletely and cyclisizes according to Example 1. When no or substantially no pentadecanolide codistils anymore with pentane triol the lactone is separated from the triol and distilled. 181 g. of pentadecanolide are obtained. Melting point 35 C. Yield 75 of the theory.
What we claim is:
1. A process for preparing a macrocyclic lactone selected from the group consisting of pentadecanolide, 12- oxa-hexadecanolide and l2-oxa-pentadecanolide, comprising the steps of heating a polymer of a hydroxy carboxylic acid selected from the group consisting of IS-hydroxy pentadecanoic acid, l-hydroxy-12-oxa-hexadecanoic acid and 15-hydroxy-12-oxa-pentadecanoic acid, in the presence of an alkaline catalyst and a trihydric alcohol selected from the group consisting of glycerol and pentane triol-1.2.5 to depolyrnerize the polymer, and removing the corresponding lactone from the reaction mixture'by codistillation with the trihydric alcohol at the rate at which it is formed. 7 V 2. The process of claim 1, wherein the alkaline catalyst is selected from the group consisting of alcoholates,
hydroxides and salts of alkali and earth'alkali metals.
3. The process of claim 1, wherein the polymer is heated in vacuum.
References Cited in the file of this patent UNITED STATES PATENTS
Claims (1)
1. A PROCESS FOR PREPARING A MACROCYCLIC LACTONE SELECTED FROM THE GROUP CONSISTING OF PENTADECONOLIDE, 12OXA-HEXADECONOLIDE AND 12-OXA-PENTADECONOLIDE, COMPRISING THE STEPS OF HEATING A POLYMER OF A HYDROXY CARBOXYLIC ACID SELECTED FROM THE GROUP CONSISTING OF 15-HYCROXY PENTADECANOIC ACID, 16-HYDROXY-12-OXA-HEXADECANOIC ACID AND 15-HYDROXY-12-OXA-PENTADECANOIC ACID, IN THE PRESENCE OF AN ALKALINE CATALYST AND A TRIHYDRIC ALCOHOL SELECTED FROM THE GROUP CONSISTING OF GLYCEROL AND PENTANE TROL 1.2.5 TO DEPOLYMERIZE THE POLYMER, AND REMOVING THE CORRESPONDING LACTONE FROM THE REACTION MIXTURE BY CODISTILLATION WITH THE TRIHYDRIC ALCOHOL AT THE RATE AT WHICH IT IS FORMED.
Publications (1)
Publication Number | Publication Date |
---|---|
US2936310A true US2936310A (en) | 1960-05-10 |
Family
ID=3449329
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
US2936310D Expired - Lifetime US2936310A (en) | Process of preparing macrocyclic |
Country Status (1)
Country | Link |
---|---|
US (1) | US2936310A (en) |
Cited By (7)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US3173925A (en) * | 1961-11-14 | 1965-03-16 | Kalk Chemische Fabrik Gmbh | Production of 4-disubstituted 1, 3-dioxolones(5) |
US3728358A (en) * | 1971-06-25 | 1973-04-17 | Int Flavors & Fragrances Inc | Process for the preparation of macrocyclic lactones |
US3953472A (en) * | 1973-03-17 | 1976-04-27 | Teijin Limited | Method for separating lactones from a mixture containing lactones |
US4136098A (en) * | 1977-04-01 | 1979-01-23 | Chemische Werke Huels, A.G. | Process for the production of cyclic esters of undecanedioic acid |
JPS57122078A (en) * | 1981-01-22 | 1982-07-29 | Nisso Yuka Kogyo Kk | Preparation of macrocyclic ethylenedioate |
US5693828A (en) * | 1996-05-09 | 1997-12-02 | International Flavors & Fragrances Inc. | Process for preparing lactones and intermediates therefor |
US11549131B2 (en) | 2018-07-17 | 2023-01-10 | Conagen Inc. | Biosynthetic production of gamma-lactones |
Citations (5)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US2020298A (en) * | 1935-11-12 | Cyclic ester | ||
GB490044A (en) * | 1937-01-04 | 1938-08-04 | Givaudan & Cie Sa | Improvements in or relating to the preparation of lactones |
US2163109A (en) * | 1936-04-03 | 1939-06-20 | Du Pont | Chemical process and products therefrom |
US2234551A (en) * | 1941-03-11 | Preparation of lactones | ||
US2417151A (en) * | 1947-03-11 | Composition of matter with a scent |
-
0
- US US2936310D patent/US2936310A/en not_active Expired - Lifetime
Patent Citations (5)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US2020298A (en) * | 1935-11-12 | Cyclic ester | ||
US2234551A (en) * | 1941-03-11 | Preparation of lactones | ||
US2417151A (en) * | 1947-03-11 | Composition of matter with a scent | ||
US2163109A (en) * | 1936-04-03 | 1939-06-20 | Du Pont | Chemical process and products therefrom |
GB490044A (en) * | 1937-01-04 | 1938-08-04 | Givaudan & Cie Sa | Improvements in or relating to the preparation of lactones |
Cited By (8)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US3173925A (en) * | 1961-11-14 | 1965-03-16 | Kalk Chemische Fabrik Gmbh | Production of 4-disubstituted 1, 3-dioxolones(5) |
US3728358A (en) * | 1971-06-25 | 1973-04-17 | Int Flavors & Fragrances Inc | Process for the preparation of macrocyclic lactones |
US3953472A (en) * | 1973-03-17 | 1976-04-27 | Teijin Limited | Method for separating lactones from a mixture containing lactones |
US4136098A (en) * | 1977-04-01 | 1979-01-23 | Chemische Werke Huels, A.G. | Process for the production of cyclic esters of undecanedioic acid |
JPS57122078A (en) * | 1981-01-22 | 1982-07-29 | Nisso Yuka Kogyo Kk | Preparation of macrocyclic ethylenedioate |
JPS6239157B2 (en) * | 1981-01-22 | 1987-08-21 | Nitsuso Yuka Kogyo Kk | |
US5693828A (en) * | 1996-05-09 | 1997-12-02 | International Flavors & Fragrances Inc. | Process for preparing lactones and intermediates therefor |
US11549131B2 (en) | 2018-07-17 | 2023-01-10 | Conagen Inc. | Biosynthetic production of gamma-lactones |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
US8106234B2 (en) | Methylidene malonate process | |
US3227764A (en) | Separation of cis and trans isomers of tetraalkyl - 1,3 - cyclobutanediols and novel compound obtained thereby | |
US5023350A (en) | Process for the purification of cyclic esters | |
US2020298A (en) | Cyclic ester | |
JPH06504762A (en) | Lactide production method by dehydration of aqueous lactic acid raw material | |
CA2427584C (en) | Process for the production of anhydrosugar alcohols | |
US2936310A (en) | Process of preparing macrocyclic | |
JPH06256340A (en) | Purification of lactide by melting and crystallization | |
AU2002224470A1 (en) | Process for the production of anhydrosugar alcohols | |
AU2015347429B2 (en) | Process for purifying a crude composition of dialkyl ester of 2,5-furandicarboxylic acid | |
KR20030069792A (en) | Method for purifying cyclic esters | |
JPH08301866A (en) | Continuous production of macrocyclic compound | |
US3188319A (en) | Production of vinyl estess | |
US3056830A (en) | Preparation of alkyl esters of sorbic acid | |
JPH0780838B2 (en) | Caprolactam manufacturing method | |
US3816525A (en) | Process for oxidation of vicinal diol groups into carboxyl groups with oxygen | |
GB1397659A (en) | Process for preparing glycidol | |
US4891436A (en) | Process for preparing bis-methylene spiroorthocarbonate | |
WO2015094895A1 (en) | An improved glycol acylation process | |
GB793555A (en) | A process for the preparation of macrocyclic lactones | |
US2379104A (en) | Manufacture of esters | |
DE1025861B (en) | Process for the preparation of macrocyclic lactones | |
US3173925A (en) | Production of 4-disubstituted 1, 3-dioxolones(5) | |
JP5212953B2 (en) | Process for producing optically active γ-lactone | |
US2443818A (en) | Oxidation of mesityl oxide with molecular oxygen |